Newswise — Scientists from the Cancer Vaccine Collaborative (CVC) have discovered that the cancer-specific protein, SSX-2, induces a spontaneous immunological reaction against cancer cells in melanoma patients, offering a new target for the development of a therapeutic melanoma vaccine. SSX-2 is the prototype of the SSX family, and is part of a larger group of proteins known as cancer/testis (CT) antigens. CT proteins are expressed in cancer cells and on normal testes, but the immune system recognizes CT antigens only when they are present on cancer cells. This exquisite immunological specificity for cancer, but not normal, cells has drawn many scientists and clinicians to investigate vaccines against CT antigens as cancer therapies.

"SSX-2 is a particularly good target for a cancer vaccine," says Dr. Danila Valmori, an Assistant Member of the Ludwig Institute for Cancer Research (LICR), and the senior author of the study. "We found that patients are mounting their own immunological responses against cancer cells expressing SSX-2, and although these spontaneously occurring immunological responses are apparently not sufficient for stopping tumor growth, possibly because they develop late in the disease progression, we think that a vaccine that stimulates and amplifies this naturally-occurring attack will have a good chance of giving a clinical response."

The CVC, which was established by the Cancer Research Institute (CRI) and LICR, had previously reported the detection of SSX-2-specific CD8+ T cells and antibodies in patients with melanoma. However, in the report published today in the Journal of Clinical Investigation, they describe the discovery of SSX-2-specific CD4+ T cells, the final member of the immunological triumvirate. Work is underway to characterize the immunogenicity of the other SSX family members, which were originally identified by LICR researchers in New York.

"We believe that for a cancer vaccine to be effective, you really need to be able to induce, and monitor, the activation of all three components of the immune system," explains Dr. Jill O'Donnell-Tormey, the Executive Director of CRI. "So with this important preclinical work complete, we can now begin early-phase trials of SSX-2 based vaccines to work out variables such as the best vaccine composition, the best dose, the best delivery methods, and so on. And because we know how to monitor the SSX-2-specific responses of T cells and antibodies, we can speed the refinement of an SSX-2 vaccine by using standardized monitoring, and investigating several vaccine variables in parallel trials at different CVC Centers."

The first early-phase clinical trial, which will assess the safety and dose profiles of an SSX-2 peptide-based vaccine, is scheduled to begin this year at the CVC Clinical Trials Center in Zürich, Switzerland.

The published study was supported by the Cancer Research Institute and sponsored by the Ludwig Institute for Cancer Research, under the auspices of the Cancer Vaccine Collaborative. The clinical component of the study was conducted at the Columbia-Presbyterian Medical Center. The CVC team was comprised of researchers from the New York Branch of the Ludwig Institute for Cancer Research at Memorial Sloan-Kettering Cancer Center, and the Departments of Cardio-Thoracic Surgery and Pathology at Weill Medical College of Cornell University.

The Cancer Vaccine CollaborativeThe Cancer Vaccine Collaborative (CVC) is a partnership between two not-for-profit academic institutions that has developed an unparalleled program that conducts a systematic analysis in humans comparing immunological approaches to the creation of therapeutic cancer vaccines through a coordinated global effort.

The Cancer Research InstituteSince its inception in 1953, the Cancer Research Institute (CRI) has had a singular mission—to foster research that will yield an understanding of the immune system and its response to cancer, with the ultimate goal of developing immunological methods for the control and prevention of the disease. To accomplish these goals, CRI supports scientists at all stages of their careers and funds every step of the research process, from basic laboratory studies to clinical trials testing novel immunotherapies. Guided by a Scientific Advisory Council, which includes 4 Nobel Prize winners and 24 members of the National Academy of Sciences, CRI awards fellowships and grants to scientists around the world. Additionally, the Institute has more recently taken on a new leadership role in the areas of preclinical and clinical research by serving as the integrating force and facilitator of collaborations among leading experts. CRI has thus become a catalyst for accelerating the development of cancer vaccines and antibody therapies.

The Ludwig Institute for Cancer ResearchThe Ludwig Institute for Cancer Research (LICR) is the largest international academic institute dedicated to understanding and controlling cancer. With ten Branches in seven countries, and numerous Affiliates and Clinical Trial Centers in many others, the scientific network that is LICR quite literally covers the globe. The uniqueness of LICR lies not only in its size and scale, but also in its philosophy and ability to drive its results from the laboratory into the clinic. LICR has developed an impressive portfolio of reagents, knowledge, expertise, and intellectual property, and has also assembled the personnel, facilities, and practices necessary to patent, clinically evaluate, license, and thus translate, the most promising aspects of its own laboratory research into cancer therapies.

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